This funding opportunity announcement (FOA) solicits
applications from institutions/organizations that propose to establish Network Group Operations Centers for the NCI National Clinical Trials Network (NCTN). The goal of the NCTN is
to develop and conduct state-of-the-art cancer treatment and advanced imaging
clinical trials, especially large, definitive multi-institutional trials
evaluating new cancer therapies and related clinical approaches for both
adult and pediatric patients. The NCTN consists of six components, each with
its own FOA, which are: Network Group Operations Centers (covered by this
FOA); Network Group Statistics and Data Management Centers; Network Group
Integrated Translation Science Support Centers; Lead Academic Participating
Site Centers; Network Radiotherapy and Imaging Core Services Centers; and a
Canadian Collaborating Clinical Trials Network.

The NCTN Network Group Operations Centers will provide
scientific leadership for developing and implementing multi-disciplinary,
multi-institutional trials in a range of cancer types and special populations
with specific scientific strategy and goals.

Key
Dates

Posted Date

July 23, 2012

Letter of Intent Due Date

December 15, 2012

Application Due Date(s)

January 15, 2013

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

June 2013

Advisory Council Review

October, 2013

Earliest Start Date(s)

March 1, 2014

Expiration Date

January 16, 2013

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in
the PHS398
Application Guide except where instructed to do otherwise (in this FOA or
in a Notice from the NIH Guide
for Grants and Contracts). Conformance to all requirements (both in
the Application Guide and the FOA) is required and strictly enforced. While
some links are provided, applicants must read and follow all application instructions
in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

This Funding Opportunity Announcement (FOA) is one of six
FOAs that reflect the comprehensive effort by the National Cancer Institute
(NCI) to transform the previous NCI-sponsored Clinical Trials Cooperative Group
Program from supporting several individually operating Cooperative Groups into
a new consolidated and integrated NCI National Clinical Trials Network (NCTN)
Program. The overall goal for the entire NCTN Program is to conduct definitive,
randomized, late phase clinical treatment trials and advanced imaging trials
across a broad range of diseases and diverse patient populations as part of the
NCI’s overall clinical research program for adults and children with cancer.
The NCTN will also conduct, as necessary, smaller developmental studies
preliminary to the definitive trials. The NCTN Program will be based on an
integrated network of clinical trials groups that will collaborate with each
other as well as with other NCTN components and other NCI-sponsored programs
and investigators.

The
NCTN Program will support the following components that will be individually
awarded through the respective FOAs indicated below:

The new consolidated structure of the NCTN is designed to
comprise five U.S. Network Groups (up to 1 pediatric group and up to 4 adult
groups) and up to 1 Canadian Network Organization. Each U.S. Network Group will
be organized around a dedicated Operations Center working with an affiliated
Statistics and Data Management Center and other NCTN components as appropriate.

Note:
An overview of the roles of individual NCTN components is outlined below. However,
it is imperative that prospective applicants read the individual FOAs for those
components for which they intend to apply.

This
FOA provides expanded information specific to the Network Group Operations
Centers and details needed to apply for a Network Group Operations Center award.

Background

For more than 50 years, the NCI has supported a standing
clinical trials infrastructure – the NCI National Clinical Trials Cooperative
Group Program (also referred to as the "Group Program") – funded
through the Division of Cancer Treatment and Diagnosis (DCTD) to conduct
large-scale, clinical treatment trials across the nation. The Group Program has
successfully completed many important trials that have led to new treatments
for cancer patients. Its activities have involved more than 3,100 institutions
and 14,000 investigators enrolling between 20,000 to 25,000 patients in clinical
treatment and advanced imaging trials each year over the past decade. The Group
Program has promoted the evaluation of multi-modality treatments and
combinations of novel agents. In addition, studies supported by Group Program
have emphasized clinical trials in members of special populations (e.g.,
children, young adults, and underserved populations) and clinical trials
focused on rare tumor types. This focus has allowed the Group Program to
complement, rather than duplicate, research supported by the private sector.

Cancer medicine has evolved in recent years into a more
molecularly-based discipline. Diagnosis is being improved through genetic
sub-classification as well as functional imaging of tumors and new treatments
are being developed aimed at specific cancer-related pathways. As part of its
effort to take advantage of new discoveries in oncologic science, NCI asked the
Institute of Medicine (IOM) in 2009 to review the NCI-sponsored Clinical Trials
Cooperative Group Program. The IOM report (http://iom.edu/Reports/2010/A-National-Cancer-Clinical-Trials-System-for-the-21st-Century-Reinvigorating-the-NCI-Cooperative.aspx)
noted that, despite its impressive record of accomplishment, the current trials
system has become less efficient, has difficulty prioritizing studies, and has
been underfunded for the number of trials that it conducts. The IOM report
recommended that the existing adult Clinical Trials Cooperative Groups be
consolidated into a smaller number of Groups, each with greater capabilities
and appropriate incentives to promote better overall system integration.
Consolidation should promote efficiency by encouraging a structural makeover of
clinical trial group operations centers and statistics and data management
centers. It should also facilitate prioritization in clinical research by
focusing trials even more than before on questions unlikely to be addressed by
the private sector.

Based on the IOM review recommendations as well as additional
input received by the NCI from stakeholders across the oncology community, the
NCI has developed a comprehensive plan to transform the previous NCI-sponsored
Clinical Trials Cooperative Group Program that funded several separate
organizations conducting cancer treatment trials into a new consolidated and
integrated Program referred to as the NCI National Clinical Trials Network
(NCTN).

Overall Goal of the NCTN Program

The overall goal of the NCTN Program is to conduct
definitive, randomized, late phase clinical treatment trials and advanced imaging
trials across a broad range of diseases and diverse patient populations, as
well as development efforts preliminary to those trials, as part of the NCI’s
overall clinical research program for adults and children with cancer.

In
order to achieve the overall goal of the Program, essential features of the
NCTN will include:

A coordinated, collaborative, and inclusive process, i.e.,
involving broad representation from the oncology community including academic
and community clinical investigators, translational science investigators,
biostatisticians, and patient advocates for generating concepts, primarily for
late phase, definitive, clinical trials to evaluate innovative cancer
treatments in specific cancers and/or with a focus on specific modalities (e.g.,
imaging, radiation, surgery);

Prioritization of trial concepts for development and conduct by
national NCI-managed disease and modality-specific steering committees composed
of leading cancer experts and advocates from the extramural community, including
Network Group representatives, as well as NCI, consistent with national
priorities for clinical cancer research;

Efficient and timely activation, conduct, and completion of
clinical trials meeting all regulatory requirements, through the effective
integration of scientific expertise and clinical trials management
capabilities; and

Incorporation of innovative science into clinical trials through
collaboration among institutions and investigators with expertise in various
medical specialties/disciplines relevant to treatment of adult and childhood
cancers (e.g., pharmacology, clinical oncology, imaging) as well as those with expertise
to integrate translational science into design and conduct of NCTN trials.

Anticipated Organization of Key Components of the NCTN
Program

In the NCTN Program, a Network Group is defined as a
clinical trials group with a dedicated Operations Center and an associated
Statistics and Data Management Center responsible for the design and
development of clinical trials as well as the conduct of trials via member
institutions/sites that enroll patients. Member sites of Network Groups include
institutions/sites that are funded either directly by the Network Group
Operations Center for their participation in NCTN trials or through other
funded key components of the NCTN (i.e., Lead Academic Participating Sites
award) or through related NCI-sponsored programs that fund participation (i.e.,
Community Clinical Oncology Program, Minority-based Community Clinical Oncology
Program). Network Groups are expected to collaborate with each other and with
NCI to achieve the overall goal of the Program. Member institutions/sites of
Network Groups will be able to enroll patients on all adult Phase 3 trials as
well as select early phase trials, irrespective of the specific Network Group
that is leading the trial. In addition, select trials for adolescent and young
adults will be open to all member institutions/sites. Network Groups will also
provide trial operations, data management, and statistical support for
approved, multi-center Phase 2 and Phase 3 trials originating outside the Network.

Each Network Group will have an integrated organizational
structure encompassing scientific leadership, statistics, clinical trial
operations, data management, and administration. Network Groups will be funded
through an Operations Center award (covering scientific leadership, trial
operations, and general administration including oversight of member
institutions/sites enrolling patients) and a separate Statistics and Data
Management Center award (covering statistical design and data management).
Organizations may also apply for a separate, integrated, translational science
support center award with support from one or more Network Groups - i.e.,
Operations Center(s) and associated Statistics and Data Management Center(s) –
to facilitate integration of translational science into the design of clinical
trials conducted by the supporting Network Group(s).

In addition to the awards described above, the NCTN
Program will involve several awards to Lead Academic Participating Sites or institutions
to support scientific leaders at those sites who are affiliated with one or
more Network Groups to provide leadership in the design and conduct of trials
as well as to support patient enrollments at their sites to NCTN trials. The
Program will also support an award for an organization to provide core services
related to incorporating appropriate quality assurance and credentialing of
radiotherapy and imaging techniques/approaches in clinical trials to all the
Network Groups and an award to sponsor a corresponding Canadian clinical trials
organization to partner with the Network Groups in the U.S. in the design and
conduct of NCTN trials.

Each of these key components of the NCTN Program is
described briefly below.

Network
Group Operations Centers: The Operations Center will provide
scientific leadership for developing and implementing multi-disciplinary,
multi-institutional trials in a range of diseases and special populations with
specific scientific strategy and goals. The scientific goals may include
strategic innovation in advanced technology for specific research areas (e.g.,
advanced imaging methods/agents, radiotherapy) and the testing of innovative
concepts and tools in prospective, multi-institutional clinical trials.
Operations Centers will be responsible for trial operations including timely
protocol development and management, compliance with FDA and OHRP regulatory
and patient protection requirements, audits, training, quality assurance, and
site support. The Operations Center is expected to be closely integrated with
the Statistics and Data Management Center in all aspects of trial operations
through jointly developed policies and procedures for clinical trial
development and conduct. The Operations Center will also be responsible for
Network Group administration, including financial management, monitoring of member
institution/site performance, coordination of biospecimen collection from
patients on clinical trials, and adherence to all applicable NIH/NCI policies
and regulations. Network Groups Operations Centers will also provide trial
operations for approved, multi-center phase 2 and phase 3 trials originating
outside the Network Group.

Network
Group Statistics and Data Management Centers: These Centers
will be responsible for providing the statistical expertise required to ensure
effective scientific design and conduct of clinical trials as well as
leadership in innovation in statistical methodology. The Centers will also be
responsible for data management, data analysis, and statistical analysis for
trials led by the Network Group (including approved, multi-center phase 2 and
phase 3 trials originating outside the Network Group) as well as for
translational and other ancillary studies associated with trials, working
closely with trial operations staff from the associated Network Group
Operations Center.

Network
Group Integrated Translational Science Centers: These awards
will provide support for leadership and expertise to facilitate incorporating
translational science into Network Group clinical trials.

Network
Lead Academic Participating Sites: These academic
institutions/sites will provide scientific leadership in development and
conduct of clinical trials in association with 1 or more adult Network Groups
as well as substantial accrual to clinical trials conducted across the entire
NCTN. The eligibility to apply for these awards is restricted to clinical
academic centers. For the purposes of this award, clinical academic centers are
distinguished from large medical centers whose primary mission is patient care,
as in addition to patient care, clinical academic centers have comprehensive
medical training programs and preclinical laboratories that perform basic
science research.

Canadian
Collaborating Clinical Trial Network: This Canadian
organization will be a non-profit clinical trials organization capable of being
a full partner with the U.S. Network in the conduct of large-scale, multi-site
clinical trials. Incorporation of a Canadian Clinical Trials Network as a
collaborating partner brings an additional advantage as U.S. Network Groups are
anticipated to have Canadian member sites. A Canadian network will be able to help
reduce duplicative regulatory staff at each U.S. Network Operations Center.

The Network Group Operations Center application must address
the following 4 required functional components:

Clinical
Trial Development Program – This functional component should
consist of a well-defined research strategy by the applicant for the
development of clinical trials in specific disease areas and patient
populations.

Member
Site Accrual Program – This functional component should consist
of a well-defined plan for accrual commensurate with the scale and goals of the
NCTN Program to clinical trials by the applicant's member institutions/sites,
both trials led by the applicant as well as trials led by other Network Groups.

Operational
Management – This functional component should describe the
applicant's organizational structure, governance, standard operating
procedures, and operational efficiency program in order to demonstrate the
applicant's capability to develop, activate, and conduct clinical trials in a
timely manner.

Program for
Collaborations and Participation in Collective Management – This
functional component should consist of a well-defined plan for potential
collaborations by the applicant with other Network Groups and NCI-sponsored
investigators and programs as well as how the applicant plans to participate in
the collective management of the NCTN.

PROGRAM
EVALUATION: The NCTN program will be subject to external
evaluation near the end of the funding period (to be coordinated by the NCI
Program Staff). Such evaluation is part of NIH efforts to optimize the
efficiency of the funded research. The evaluation process will involve
monitoring and assessing the progress of the NCTN toward achieving its goals.
This aspect includes evaluating the quality, value, and scientific impact of
the clinical trials and other research activities conducted by the NCTN,
timeliness of clinical trial development and completion, efficiency of
operations, effort integration, and collaborations across the Network, and
interactions with other relevant NCI-sponsored organizations and programs. For
the efficient evaluation of the NCTN Program, cooperation of all the NCTN
awardees (for all types of the NCTN components) will be important and expected.

Section II. Award Information

Funding Instrument

Cooperative Agreement

Application Types Allowed

New

The OER
Glossary and the PHS398 Application Guide provide details on these application
types.

Funds Available and Anticipated Number of Awards

The National Cancer Institute intends to commit an
estimated total of $90 million for up to 5 awards (up to 1 pediatric and up
to 4 adult Network Group Operations Centers in FY 2014). Future amounts will
depend on annual appropriations.

Award Budget

Application budgets are not limited, but need to reflect
actual needs of the proposed project. Because the nature and scope of the
proposed research will vary from application to application, the size of each
award will vary.

Award Project Period

5 years

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible
to apply.
Foreign components, as defined in the NIH
Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations
as described in the PHS398 Application Guide to be eligible to apply for or
receive an award. Applicants must have a valid Dun and Bradstreet Universal
Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due
date. Applicant organizations are strongly encouraged to start the registration
process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

With the restrictions defined below any individual(s) with
the skills, knowledge, and resources necessary to carry out the proposed
research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is
invited to work with his/her organization to develop an application for
support. Individuals from underrepresented racial and ethnic groups as well as
individuals with disabilities are always encouraged to apply for NIH support.

However, an individual who is designated as a PD/PI on the
application for a Network Group Operations Center can, if appropriate, be
listed as key personnel on the application for its associated Network Group
Statistics and Data Management Center and/or on the application for the Network
Radiotherapy and Imaging Core Services Centers (RFA-CA-12-014),
but not on the other applications listed above and not on applications for
other Network Group Statistics and Data Management Centers.

Each applicant organization may submit only one application
in response to this FOA. An organization applying for the Network Group
Statistics and Data Management Center award under RFA-CA-12-011 or for the Network Radiotherapy and Imaging Core Services Center award under RFA-CA-12-014 cannot apply for a Network Group Operations Center award under this FOA.

Section IV. Application and Submission Information

1. Address to Request
Application Package

Applicants are required to prepare applications according to
the current PHS 398 application forms in accordance with the PHS 398
Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the PHS398
Application Guide, except where instructed in this funding opportunity
announcement to do otherwise. Conformance to the requirements in the
Application Guide is required and strictly enforced. Applications that are out
of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows NCI staff members to estimate the potential review
workload and plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application,
including the checklist, and three signed photocopies in one package to:

All page limitations described in the PHS398 Application
Guide and the Table of
Page Limits must be followed, with the following exceptions or additional
requirements: Section 3 - Research Strategy of the PHS 398 Research Plan must
consist of the new sub-sections A-E with the following individual page limits
as noted below.

A. Operations Center Overview - 12 pages

B. Clinical Trial Development Program - 30 pages

C. Member Site Accrual Program– 12 pages

D. Operational Management - 12 pages

E. Program for Collaborations and Collective Management -
12 pages

Resources Section

In addition to standard information, provide in this section
documentation of important capabilities and available resources as indicated
for specific functional components of the Network Group Operations Centers
below. Relevant information may be provided in tabular form as listed below. Applicants
are strongly encouraged to use, as appropriate, table templates provided in Part
4 - Appendices - Section II.A. of the Guidelines document for the NCTN Program
(http://ctep.cancer.gov/investigatorResources/default.htm#guidelines_policies).

In this section, applicants are expected to provide a
general overview of the proposed Operations Center and describe the general
features and operations of the Center. Include a diagram illustrating the
organizational structure of the proposed Operations Center and outline how the
Operations Center would interact with the other key components of the NCTN Program.

Sub-Section
B. Clinical Trial Development Program (up to 30 pages)

In this section, applicants are expected to address the
following aspects:

Research Directions. Define
the overall research directions for the development of clinical trials in
specific disease areas and patient populations. In particular, the applicant team
must identify the diseases that the proposed Operations Center will pursue in
its research and outline how its particular research objectives will benefit
the NCTN Program as a whole. The applicant team should also address how its
research strategy will address unmet clinical needs in rare cancers.

Capabilities and Experience. Summarize the capabilities and experience of the applicant team in successfully
developing, organizing, and coordinating large-scale, definitive clinical
trials as well as experience in leveraging resources from multiple funding sources
for the conduct of ancillary studies (e.g., correlative science studies)
associated with clinical trials. Outline the most important achievements in these
areas over the past 5-6 years.

Promising Directions.Identify the most
promising current and future research initiatives and clinical trials as an
indication of the potential of the applicant team to contribute to the NCTN
Program. It is expected that applicants' emphasis will be placed on studies with
potential to change clinical practice and the importance of the overall
research strategy being pursued and not on individual disease clinical trial
portfolios.

Role of Senior Members of Research
Teams. Include information on the current participation of senior
members of applicant’s research teams in relevant committees (e.g., scientific
research committees and administrative committees). Outline the current
situation and plans for the involvement of senior members in the mentoring of new/junior
investigators in clinical trial research.

NOTE: Information on the applicant’s scientific leadership in clinical trial
development as well as achievements of its past (over the prior 5 to 6 years) and
current clinical trial development program may be summarized in tables as
described in the Resources Section above.

Sub-Section
C. Member Site Accrual Program (up to 12 pages)

This functional component is
critical for the role of the Operations Center. Include in this sub-section a well-defined
plan for robust accrual of patients to NCTN clinical trials. In this plan,
describe how the Operations Center will work with the member institutions/sites
of clinical trials that are or will be affiliated with the applicants. This
plan must encompass accrual to clinical trials led by the applicant as well as
trials that may be led by other Network Groups. Emphasis should be placed on overall
accrual to the NCTN not on accrual specific to trials led by the Network Group
Operations Center.Summarize the potential of the proposed Operations Center to
accrue (via its member institutions/sites) patients to oncology clinical
treatment trials and advanced imaging trials in a publicly funded clinical
trials system across a broad range of diseases, including rare cancers.

NOTE: In this sub-Section, the applicants are expected to highlight the
track record of the applicant team and its member sites for accrual over the
past 5-6 years, in addition to details presented in accrual summary tables to
be included under "Resources", as indicated above.

Sub-Section
D. Operational Management (up to 12 pages)

In this section, address the organizational structure of the
proposed Operations Center, its governance, standard operating procedures, and
operational efficiency program. All these elements are expected to be designed
to optimize the applicant's capability to develop, activate, and conduct
clinical trials in a timely manner. Specifically, address the following
aspects:

Governance
& organizational structure of leadership team for the Operations Center.
Define the roles and responsibilities of the PD(s)/PI(s), including
responsibilities for human subjects in clinical studies. If applicable, outline
in this sub-Section a rationale and the general benefits of choosing a multiple
PD(s)/PI(s) approach. NOTE: Applicants designating multiple PD(s)/PI(s) must also complete the dedicated
Section 12 of PHS 398 Research Plan "Multiple PD/PI Leadership Plan."

Scope
and authority of the applicant's leadership team. Delineate the
roles of other key members of the leadership team in terms of scientific,
administrative, and/or technical responsibilities, as appropriate, such as the
Director of Operations position and the Executive/Advisory Committee. Outline
communication plans, processes for making decisions on scientific directions,
and procedures for resolving conflicts. Include succession plans for key
leadership positions and describe the relationship/rules for institutional
membership in the Network Group as well as financial management policies.

Operational
efficiency. Describe plans to optimize the operational efficiency
in both study development and clinical trial activation, including providing appropriate
training programs for protocol chairs, institutional site PDs/PIs, and clinical
research associates (CRAs). Indicate how the proposed Center will take
advantage of the available, NCI-supported standard tools and services for the
conduct of clinical trials (e.g., Clinical Data Management System, Oncology
Patient Enrollment System, and Regulatory Support System for the NCTN). Address
how the proposed Center will assure the compliance with NCI/NIH and other Federal
regulations regarding study monitoring and clinical research (e.g., explain how
these aspects are covered by the applicants’ policies on Data Safety and
Monitoring, Data Sharing, Biospecimen Sharing, and Onsite Auditing).

The applicant should also present a plan and demonstrate its
ability to adhere to regulations regarding trial registration in the NCI Clinical
Trials Reporting Program and in the U.S. National Library of Medicine (NLM) (www.clinicaltrials.gov) along with
results reporting, as applicable. The applicant should also describe its plan
to ensure that results from clinical trials will be published in peer-reviewed
manuscripts in a timely manner consistent with NCTN Program requirements and
demonstrate its potential to do so. The applicant should also describe its
plans for and demonstrate its capability to make data and biospecimens from
clinical trials accessible to the public for further research or explain why
sharing is not possible.

The applicant’s key standard operating procedures for the
conduct of clinical trials related to the following may be provided in the
Resource section of the application:

NOTE: The
applicants' capabilities and potential to conduct large-scale operations
related to developing, activating, and conducting clinical trials are essential
and will be a factor in the application merit evaluation. In this sub-Section,
the applicants are expected to highlight their most relevant achievements over
the past 5-6 years, in addition to details presented in summary tables to be
included under "Resources", as indicated above.

Sub-Section E. Program for
Collaborations and Participation in Collective Management (up to 12 pages)

In this section, address the
following aspects:

Highlight the current collaborative interactions of the applicant
team related to clinical trials and translational research with investigators
at other clinical trial organizations as well as other NCI-sponsored programs;

Define specific plans for future joint activities and potential
collaborations between investigators at the proposed Operations Center and
investigators at other Network Groups; and

In addition, address the potential
of the applicant team to participate in the collective management of the NCTN
and relevant experience in the past 5-6 years:

Outline expectations of how your team will participate in the
collective management of the NCTN;

Provide specific examples of participation by member
investigators of the Network Group Operations Centers in the NCI Scientific
Steering Committees (SSC) and associated Task Forces and Working Groups, Planning
Committees for SSC Clinical Trials Planning, and NCI Central Institutional
Review Board (Central IRB) (including membership of institutional members of
the Network Group on the NCI Central IRBs) and/or examples of similar collaborative
activities involving other clinical trial networks; and

Discuss the ability of the team to complete development of study
proposals and conduct future clinical trials that may originate outside the Network
Group Operations Center if they are approved by the NCI disease-specific SSCs.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398
Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan. A model for a
Data Sharing Plan for Network Group Operations Centers and associated Network
Group Statistics and Data Management Centers for the NCTN Program is provided
in Part 4 - Appendices - Section VII in the Guidelines document for the NCTN
Program (http://ctep.cancer.gov/investigatorResources/default.htm#guidelines_policies).

Applications must be received on or before the due dates in Part I. Overview Information. If an
application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for
completeness by the NIH Center for Scientific Review and responsiveness by the NCI. Applications that are
incomplete and/or nonresponsive will not be reviewed.

Awardees must agree to the "Cooperative Agreement Terms
and Conditions of Award" in Section VI. "Award Administration
Information." The applicant should review the Cooperative Agreement Terms
and Conditions of Award prior to preparing the application as these terms
include information and clarifications needed by the applicant to understanding
the complete requirements of a Network Group Operations Center award.

Note on Section “Inclusion of Women, Minorities, and
Children”:

Information on the targeted/planned enrollment for
minorities and members of both genders as well as children, if applicable,
should be based on accrual summarized across all diseases for the planned
project period, not on a study or disease-specific basis.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115. Note: Because applications submitted in response to this FOA have only one due date,
applicants may submit materials per the exceptions list provided in NOT-OD-10-115 using the specified page limits.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, the emphasis is on the capabilities and
experience of the applicant team in successfully developing, organizing, and
coordinating large-scale definitive clinical trials. As all applications
submitted in response to this FOA will be “new” applications, those aspects
will be largely evaluated based on the prior performance and productivity of
the applicants. These capabilities and commensurate performance/productivity
must be appropriate and consistent with specific requirements stated in this
FOA. The required capabilities and experience are expected to reflect the
properly documented successful performance of the applicant team under the
former NCI National Clinical Trials Cooperative Group Program or equivalent
large-scale NIH or other non-profit clinical trials networks or programs in the
last 5-6 years. Reviewers will be using this information as benchmarks in
evaluating all aspects of the application, including plans for the specific
components of the proposed NCTN Operations Center and its overall scientific
potential.

Overall Impact - Overall

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the proposed Network Group
Operations Center to exert a sustained, powerful influence on the research
field(s) involved, in consideration of the following review criteria and
additional review criteria (as applicable for the Network Group Operations
Center proposed).

Scored Review Criteria - Overall

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a proposed Network Group Operations
Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed Network Group Operations Center
address an important problem or a critical barrier to progress in the field? If
the aims of the proposed Network Group Operations Center are achieved, how will
scientific knowledge, technical capability, and/or clinical practice be
improved? How will successful completion of the aims change the concepts,
methods, technologies, treatments, services, or preventative interventions that
drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the proposed Network Group Operations Center and its
research strategy? If Early Stage Investigators or New Investigators, or in the
early stages of independent careers, do they have appropriate experience and
training? If established, have they demonstrated an ongoing record of
accomplishments that have advanced their field(s)? Given that the NCTN Operations
Centers will be involved in collaborative activities (and irrespective of
whether the applicants choose to use the multi-PD/PI option), do the
investigators have complementary and integrated expertise; are their leadership
approach, governance and organizational structure appropriate for the proposed
Network Group Operations Center?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the proposed Network
Group Operations Center? Are potential problems, alternative strategies, and
benchmarks for success presented? If the project is in the early stages of
development, will the strategy establish feasibility and will particularly
risky aspects be managed?

Are the plans for 1) protection of human subjects from research risks, and 2)
inclusion of minorities and members of both sexes/genders, as well as the
inclusion of children, justified in terms of the scientific goals and research
strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the clinical research conducted by the
Network Group Operations Center benefit from unique features of the scientific
environment, subject populations, or collaborative arrangements?

Additional Scored
Review Criteria

In
addition to the above review criteria, the following additional Criteria A-D will
be applied in the determination of scientific merit and the impact/priority
score:

A. Clinical Trials Development Program;

B. Member Site Accrual Program;

C. Operational Management; and

D. Program for Collaborations and Participation in
Collective Management of NCTN.

Reviewers
will consider each of the additional review criteria below in the determination
of scientific merit, and give a separate score for each.

A. Clinical Trial Development Program

(Note: The entire Criterion A will
receive one individual score; the subcategories and aspects listed will be
assessed but not scored separately).

Significance

Overall
Research Strategy: How well does the applicant's research
strategy reflect an integrated scientific approach within oncology disease
areas as well as across disease areas? Does the research strategy address
important unmet clinical needs? Is the research strategy sufficiently practical
and feasible? Are the disease areas included in the applicant’s overall
research strategy appropriate and beneficial to the NCTN? How well would the
applicant team contribute to the development of clinical trials for patients
with rare cancers and how well would the applicant address underserved patient
populations through trials that it leads or participates in across the NCTN?

Quality
of Clinical Trials: Based on the clinical trials currently being conducted as
well as those proposed, what is the likelihood that the applicant's team can contribute
meaningfully to the goals of developing and implementing
multi-disciplinary, multi-institutional trials in a broad range of cancer types and
special populations?

Do
the trials contain important integral and integrated translational science
research questions that are appropriate and well justified? To what degree do
their results reflect qualitatively new knowledge that advances the field and may
inspire future clinical trials? Will (or have) the results lead (led) to
meaningful practice changes for cancer care or other meaningful results (e.g., Phase
2 trials leading to Phase 3 trials conducted by government or private sector,
provision of important toxicity or dosing information)? Does the applicant team
have effective mechanisms for promoting timely presentation and publications of
the results of clinical trials and associated studies?

Investigator(s)

Senior
Group Leadership for Clinical Trials Development: How well can
the PD(s)/PI(s) and the entire team of investigators assembled by the applicant
provide scientific leadership for state-of-the-art early and late phase
clinical trials in adults and/or children with cancer? Will these investigators
be able to work as a cohesive research team to efficiently and expeditiously
develop and conduct NCTN clinical trials? Does the applicant have appropriate
and clearly defined succession and transition plans for the senior leadership
of the proposed Network Group Operations Center? Does the applicant have
reasonable and appropriate limitations on terms for senior leadership that
encourage rotation of leadership responsibilities?

Scientific
Research Committee Leadership: Do the research experience and
qualifications of the leadership of the applicant's Scientific Research
Committees provide multi-disciplinary representation (e.g., medical oncology,
radiation oncology, imaging, surgery, pathology, translational science, patient
advocacy) across a broad range of oncology diseases appropriate to the stated
research goals? Does the leadership of the scientific committees have a track
record of successful multi-institutional early phase and especially late phase
clinical trials research as evidenced by publications? Do the Scientific
Research Committees provide leadership opportunities for a broad range of
investigators and are there reasonable and appropriate limits on terms for
senior leadership of the Scientific Research Committees that encourage rotation
of leadership responsibilities and provide continuity and stability in the
Committees?

Administrative
Committee Leadership: Are the experience and qualifications of
the leadership of the applicant's Administrative Committees appropriate for
development and oversight of the administrative management categories needed
for conducting both early phase and especially late phase, multi-institutional,
clinical trials (e.g., support functions for trials including involvement of
patient advocates, support programs for enrollment of members of underserved
patient populations, financial management)?

Innovation

Innovation
in Early and Late Phase Clinical Trials: Within the confines of
the ethical constraints applicable to early and late phase clinical trials for
oncology patients, does the applicant propose novel or improved ways and/or
methods to enhance or better serve its overall research strategy and the goals
of developing and implementing multi-disciplinary, multi-institutional trials
in a range of cancer types and special populations with specific scientific
strategy and goals.?

Approach

Approach
to Clinical Trial Development: Are the overall strategy,
methodology, and analyses well-reasoned and appropriate to accomplish the
specific clinical aims of the applicant? Are potential problems, alternative
strategies, and benchmarks for success presented for specific clinical trials?

Environment

Leveraging
Resources to Support Research: How successful are the members
of the applicant team in obtaining other funding (from NCI, other governmental
agencies, industry, charitable foundations, etc.) for the conduct of integral
and integrated translational research and other ancillary studies related to
their clinical trials?

New
& Junior Investigator Leadership Mentoring/Training: Does
the applicant team have in place an adequate mentorship/training program for
new and junior investigators that provides opportunities for leadership of
clinical trials (e.g., developing concepts for trial proposals, serving as
study chairs for trials, participating in scientific committees in support or
leadership roles, participating in other clinical trial activities) at
appropriate levels as well as the potential to provide opportunities to these
investigators to participate in the future in NCTN activities or initiatives?

B. Member Site Accrual Program

(Note: The entire Criterion B will receive one individual score; the aspects listed
will be assessed but not scored separately).

Accrual
Potential: Given its past record of accrual, does the applicant
have the potential to provide substantial accrual to clinical trials conducted
across the NCTN as a whole, especially in the applicant's stated areas/diseases
of research interest? Does the applicant team have the potential to contribute
to accrual of minority and underserved patient populations to trials at an
appropriate level? Doethe applicant's member institutions/sites have the
potential to contribute to accrual of patients to NCTN clinical trials in rare
tumors as needed for the NCTN goals? Does the applicant's membership appear
able to accrue to trials for rare subset populations of more common cancers?
Does the applicant demonstrate the ability to meet protocol-specified accrual
goals in a timely manner for trials it conducts? Are the PDs/PIs,
collaborators, and other researchers who comprise the scientific and technical
leadership team for this application well suited to help drive accrual for NCTN
trials?

Accrual
Monitoring: Have the applicant and its member
institutions/sites developed novel means to assess accrual potential to
clinical trials? How good are the applicant's systems/procedures to rapidly
assess and monitor accrual and implement appropriate corrective action plans if
accrual is lagging at a specific site or across all sites? Do the applicant's
member institutions/sites demonstrate high levels of biospecimen collection in
conjunction with clinical trials indicating the potential to contribute to
biospecimen collection in NCTN trials?

Member
Institution/Site Support for Accrual: How will the scientific
and administrative environment of the applicant's member institutions/sites
contribute to the probability of accrual success? Are the institutional
support, equipment and other physical resources available at member
institutions/sites adequate for the level of accrual proposed? How will accrual
to NCTN trials benefit from unique features of the scientific environment, patient
populations, and/or collaborative arrangements with other organizations
provided by applicant's member institutions/sites?

C. Operational Management

(Note: The entire Criterion C will receive one individual score; the aspects listed
will be assessed but not scored separately).

Operational
Structure, Policies, and Procedures: Are the organizational
structure and management policies of the proposed Network Group Operations Center
clear and appropriate? Does the applicant incorporate procedures and tools that
enhance coordination and productivity of operational activities including
protocol development? Does the staffing plan for the proposed Network Group
Operations Center provide appropriate and clearly defined position descriptions
and qualifications and is it adequate for required activities? Does the applicant
propose sound financial management policies and procedures for grant
administration, subcontracting with collaborating organizations, purchase
service agreements for member institutions/sites, and other related activities
(e.g., laboratory testing needed for specific clinical trials)?

Governance: Does the applicant team define a clear governance structure for the proposed
Network Group Operations Center? If the application includes multiple PD(s)/PI(s),
(is it clear how activities and responsibilities will be carried out among the
multiple PD(s)/PI(s) and is the delineation of responsibilities appropriate? Are
the scope and authority of the senior leadership, Director of Operations
position, and Executive/Advisory Committee for the proposed Network Group
Operations Center clearly and appropriately addressed? How comprehensive are
the expertise and experience of the applicant's senior administrative
management team? Are the background and expertise of the proposed Director of
Operations appropriate to oversee the operational management of the Group? Are the
policies and procedures for institution/site membership clear and appropriate
for the NCTN Program? Are the proposed operating procedures for interactions with
member institutions/sites appropriate?

If the applicant proposes to include international
institutions/sites as full members of the Network Group Operations Center, does
the applicant have appropriate monitoring plans for these sites as well as
performance assessment monitoring to ensure that the NCTN-supported activities meet
the same requirements regarding conduct of clinical trials expected of a full
U.S. member institution/site? If the applicant plans to enrolls patients on trials that
are led by non-NCTN international clinical trials organizations, does the
applicant propose appropriate policies and procedures to comply with the
applicable regulations and requirements defined in the Terms and Conditions of
the Award for a Network Group Operations Center?

Clinical
Trial Operations - Development: Are the structure and
composition of trial proposal and protocol development teams proposed by the
applicant appropriate? How well does applicant's proposed trial proposal and
protocol development process mesh with NCI standard tools and services,
including use of Common Data Elements and standard Case Report Form modules? How
appropriate are the proposed Network Group Operations Center's policies and standardized
procedures for development and monitoring of trial proposals and protocols
(including its tracking and project management systems) for ensuring that the
applicant would meet NCI-mandated trial activation timelines for operational
efficiency (i.e., Operational Efficiency Working Group [OEWG] timelines)?

Clinical
Trial Operations – Conduct: How appropriate are the proposed
Network Group Operations Center's policies for timely and efficient development
and processing of protocol amendments, including timely communication of new
safety information and amendments to member institutions/sites? Are appropriate
communications policies proposed to support the work of the scientific research
and administrative committees, coordinate activities with the associated
proposed Network Group Statistics and Data Management Centers as well as member
institutions/sites and the NCI Cancer Trials Support Unit (CTSU) related to
trial conduct? Does the applicant propose appropriate training programs for
protocol chairs, institutional site PDs/PIs, and CRAs? Does the proposed
Network Group Operations Center have appropriate key standard operating
procedures related to a Data and Safety MonitoringBoard Policy for Phase
3 trials and randomized Phase 2 trials, Data and Safety Monitoring Plans for phase
1 and Phase 2 trials, Conflict of Interest Policies, and a standard
template for the Informed Consent Document for clinical trials that are in
compliance with NCI/CTEP, NIH, and federal regulations?

Compliance/Quality
Assurance/Auditing: How well do the applicant's proposed policies
and procedures for clinical trial conduct comply with good clinical practice,
including all Federal/HHS/NIH/NCI requirements related to clinical trial
research with human subjects, as well as with NCI/DCTD requirements related to
NCI/DCTD Intellectual Property policy, NCI/DCTD Cooperative Research and Development Agreements for
clinical trials conducted under an NCI

Investigational New Drug (IND) or
Device Exemption (IDE) or other NCI binding collaborative agreement? How
appropriate are the applicant's plans to ensure the quality assurance of
clinical trial data and collection of biospecimens? How appropriate are the
applicant's proposed policies and procedures in meeting the onsite audit requirements
of the NCI Clinical Trials Monitoring Branch Guidelines (CTMB) for its member
institutions/sites? How appropriate are the applicant's plans to appropriately
address issues with member institutions/sites noted at the time of audit,
including non-compliance, data quality, data reporting requirement, and
timeliness of audits and re-audits? Does the applicant propose a quality
assurance program with its associated Statistics and Data Management Center
that is adequately proactive in terms of ensuring ongoing quality control of
data during trial conduct?

D. Program for Collaboration
& Participation in Collective Management

(Note: The entire Criterion D will receive one individual score; the aspects listed
will be assessed but not scored separately).

Collaborations
with NCTN Network Groups, NCTN Programs/Initiatives, and other NCI-sponsored
Programs/Investigators: Does the applicant have a track record
for collaborations with other trial organizations and other NCI-sponsored
programs and investigators (e.g., SPORE awardees, NCI Cancer Centers, R01/P01
investigators) on clinical trials and translational science studies that
demonstrates its potential for collaboration within the NCTN Program? Has the
applicant demonstrated that it has the capacity to conduct clinical trials that
come from investigators outside its own organization?

Collective
Management Activities: Does that applicant have a track record
that demonstrates that the members of it scientific leadership teams (i.e.,
scientific research committee members) actively participate in or can actively
contribute to NCI-supported clinical trial activities (e.g., disease-specific Scientific
Steering Committees and related task forces or working Groups, Clinical Trials
Planning Committees for meetings supported by the NCI disease-specific Steering
Committees, membership on the NCI Central IRB, participation in other NCI
programs and initiatives related to clinical research)? Do Group members
participate as members of the NCI Central IRBs? Do Group members participate in
the onsite auditing program for the Network Group Operations Center?

Additional Review Criteria - Overall

As applicable for the clinical research that the Network
Group Operations Center has proposed, reviewers will evaluate the following
additional items while determining scientific and technical merit, and in
providing an overall impact/priority score, but will not give separate scores
for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

Since the proposed Network Group Operations Centers
will involve clinical research, the committee will evaluate the proposed plans
for inclusion of minorities and members of both genders, as well as the
inclusion of children. For additional information on review of the Inclusion
section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations - Overall

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign
Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by an appropriate Scientific Review Group, convened by the NCI in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response
to this FOA.

Applications will be assigned to the NCI and will compete
for available funds with all other recommended applications submitted in
response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the National Cancer Advisory Board. The
following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (HHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.

The
PD(s)/PI(s) will have the primary responsibility for:

·
Development of an overall research strategy for the development
of clinical trials for the NCTN Program as well as all key components related
to the conduct of approved clinical trials. The awardees’ programmatic
responsibilities for the conduct of the clinical research supported under the
Cooperative Agreements are described in the documents listed below and
subsequent modifications of these documents. These documents are incorporated
by reference as program-specific Terms and Conditions of Award:

Throughout these Terms and Conditions of Award, “Network Group
Operations Center” refers to the organizational structure which is composed of
the key personnel (including the scientific and administrative leaders of the
Center and its scientific research and administrative committees) and the
member institutions/sites (including the institution/site physicians and
clinical research associates), responsible for implementing clinical trials and
collaborating on research goals of the NCTN Program through the Network Group
Operations Center. In addition, throughout these Terms and Conditions of Award,
“Network Group Operations Center,” refers to all of its member institutions/sites
no matter how the membership is defined by a particular Network Group
Operations Center.

Awardees will retain custody of and have primary rights to the
data and software developed under these awards, subject to Government rights of
access consistent with current DHHS, PHS, NIH, and NCI policies and within the
limits of any accepted binding NCI/NIH collaborative agreements with
biotechnology and pharmaceutical partners and as governed by NCI-approved Data
Sharing Plans and NCI-approved review for use of biospecimens collected in
association with NCTN trials.

Awardees are allowed to accept funds
from non-governmental sources to support NCTN research that is not supported in
part or in full by the NCI. These funds are considered “Program Income” (e.g.,
additional per case data management funding supplementing the NCI/DCTD per case
data management funding, support for correlative science studies that use
biospecimen or image collections funded by the NCI/DCTD for trials under the
NCTN Program) and must be reported under the Terms and Conditions of Award for
the NCTN Program unless they are associated with an exempted category under the
NIH grant policy for program income, available at: http://grants.nih.gov/grants/policy/nihgps_2011/nihgps_ch8.htm#_Program_Income.

All key components of the NCTN Program must report these funds to
the NCI on an annual basis (in the non-competing Type 5 application – the
annual progress report) and must indicate the clinical trial that the funds are
being used to support (or other functional component if the funds are not
provided to support specific trials). The Terms and Conditions of Award for
all the Cooperative Agreements under the NCTN Program define the operational
principles under which the awardees must function to ensure the independence of
the research conducted regardless of whether program income is or is not
available for any of the awards.

NIH
staff have substantial programmatic involvement that is above and beyond the
normal stewardship role in awards, as described below:

An NCI Program staff member(s) acting as a Project
Scientist(s) will have substantial programmatic involvement that is above and
beyond the normal stewardship role in awards, as described below. Additional
NCI staff members may be designated to have substantial involvement (e.g., in
the role of Project Coordinators). The NCI Project Scientist(s)/Coordinator(s)
will not attend peer review meetings of renewal (competing continuation) and/or
supplemental applications. If such participation is deemed essential, these
individuals will seek NCI waiver according to the NCI procedures for management
of conflict of interest.

Additionally, an NCI program director acting as Program
Official will be responsible for the normal scientific and programmatic
stewardship of the award and will be named in the award notice. Some Program
Officials may also have substantial programmatic involvement (as Project
Scientists/Coordinators). In that case, the individual involved will not attend
peer review meetings of renewal (competing continuation) and/or supplemental
applications or will seek NCI waiver as stated above.

The
main NCI responsibilities are related to research efforts of
the Network and include but are not limited to the following activities:

Responsibilities as a drug sponsor for investigational agent or
device development for NCI-sponsored or co-sponsored IND and/or IDE clinical
trials;

Serving as scientific liaisons to awardees of key components of
the NCTN Program and participation in scientific meetings of the key
components;

Oversight of data and safety monitoring plans and boards for NCTN
clinical trials;

Oversight of data management and monitoring programs for NCTN
trials as well as onsite auditing programs and quality assurance programs for the
NCTN Program, including oversight of core services for radiotherapy and imaging
supporting NCTN trials;

Facilitating coordination of the clinical trial activities and
collaborations between the Network and other NCI-sponsored programs and
investigators;

Facilitating the evaluation of clinical trial concepts and
protocol development as well as review of correlative science study requests
for use of biospecimens collected in association with NCTN trials;

Ensuring compliance with FDA requirements for investigational
agents and ensuring compliance with OHRP and other federal requirements and
regulations for research involving human research subjects;

Advising awardees concerning mechanisms established for quality
control of therapeutic and diagnostic modalities; and

Monitoring the progress and performance of this key component of
the NCTN Program.

The NCI will have access to all data (including imaging
data) collected and/or generated under this Cooperative Agreement and may
periodically review the data. The NCI may also review all records related to
awardees’ performance under the award for appropriate collection, review, and
distribution of biospecimens collected in association with NCTN trials.

In case of insufficient patient accrual per the protocol
specified timelines and/or NCI/DCTD slowly accruing guidelines for trials,
inability to meet the scientific aims of the Cooperative Agreement, or
noncompliance with the Terms and Conditions of Award, the NCI reserves the
right to reduce award budget, withhold support, suspend or terminate the award.

Areas
of Joint Responsibility include:

General aspects of collaboration on study development and conduct
especially with respect to compliance with federal regulations for clinical
trial research (and with respect to ensuring that when new avenues of cancer
therapy involving investigational drugs are pursued, trials are designed, when
appropriate, such that the clinical information obtained would be acceptable to
the FDA for inclusion in a potential licensing application), conduct of Data
and Safety Monitoring Boards for Phase 3 trials and randomized Phase 2 trials,
development of collaborative trials and international trials, collective
management of the NCTN including participating in the NCTN Leadership
Management Committee that makes recommendations to NCI for modifications to the
Program as well as to standard NCTN common tools and services.

Review of recommendations from the NCI Clinical Trials and
Translational Research Advisory Committee (CTAC) on strategic directions for
the NCTN Program.

The joint programmatic responsibilities for the awardees of the
key components of the NCTN and the NIH staff are completely described in NCI
National Clinical Trials Network (NCTN) Program Guidelines available at: http://ctep.cancer.gov/investigatorResources/default.htm#guidelines_policies with the "Collaborative
Responsibilities (Awardees of NCTN Key Components and NCI/DCTD)" described
in detail in Part 1 - Section IV.D. of the Guidelines document.

Dispute
Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution, except for areas of dispute
that are already addressed by the appeal process within the Terms and
Conditions of Award for decisions regarding approval of NCTN study proposals
and the types of studies supported by the NCTN Program as described in detail
under "Appeals Process for Decisions Regarding
Study Proposals & Types of Studies Performed by NCTN Program" in
Part 1 – Section IV.E. of the NCI National Clinical Trials Network (NCTN)
Program Guidelines (http://ctep.cancer.gov/investigatorResources/default.htm#guidelines_policies).

For other scientific and programmatic matters that are not
covered by the appeals process, a Dispute Resolution Panel composed of three
members will be convened. It will have three members: a designee of the Network
Group representatives on the NCTN Leadership Management Committee chosen by
them without NIH staff voting, one NIH designee, and a third designee with
expertise in the relevant area who is chosen by the other two. In the case of
individual disagreement, the first member may be chosen by the individual
awardee.

The appeals process and this special dispute resolution procedure
do not alter the awardee's right to appeal an adverse action that is otherwise
appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS
regulation 45 CFR Part 16.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in theNIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of applicable
NIH grants and cooperative agreements are required to report to the
Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and
welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.